1. Field of the Invention
The present invention relates to a method of preparing oxoquazepam which is an intermediate material for quazepam shown by the following formula (3) which is important in medicines such as sedatives. ##STR1##
2. Description of the Background
Oxoquazepam is considered to be prepared by the trifluoroethylation of 7-chloro-1,3-dihydro-5-(2-fluorophenyl)-2H-1,4-benzodiazepin-2-one as shown by the following formula. ##STR2##
However, trifluoroethylation of this compound does not proceed due to the strong attraction to electrons of a fluorine atom when using conventional halides such as 2,2,2-trifluoroethyl iodide.
Perfluoroalkylsulfonate which possesses higher reactivity, specifically, 2,2,2-trifluoroethyl perfluoro-n-butanesulfonate has been found as a trifluoroethylation agent instead of such conventional halides (Japanese Patent Publication No. 60663/1990).
However, 2,2,2-trifluoroethyl perfluoro-n-butanesulfonate used as the trifluoroethylation agent is a special compound which cannot be produced on an industrial level and is expensive.
The use of anhydrous polar neutral solvents such as dimethylformamide, dimethylsulfoxide, dimethylacetamide, sulfolane, or mixed solvents of these solvents with other solvents such as hydrocarbons (for example, benzene or toluene), halogenated hydrocarbons (for example, methylene dichloride or chloroform), and ethers (for example, diethyl ether or dioxane) has been disclosed as an effective method of the trifluoroethylation reaction using 2,2,2-trifluoroethyl perfluoro-n-butanesulfonate (Japanese Patent Publication No. 24807/1990). Such a solvent is used to promote N-alkylation reaction in the reaction involving a compound containing both an amine and a carbonyl group, because the ratio of N-alkylation to O-alkylation is controlled by the polarity of a reaction medium in such a reaction.
Oxoquazepam used as an intermediate material for medicines must include only a small amount of impurities, in particular, only a small amount of analogous materials. Therefore, a method of preparing high purity oxoquazepam with a high yield has been demanded.
Accordingly, an object of the present invention is to provide a method of preparing high purity oxoquazepam with a high yield using a trifluoroethylation agent which is readily available and cheap.
In view of the above-described situation, the present inventors have conducted extensive studies. As a result, the present inventors have found that high purity oxoquazepam can be prepared at high yield by the trifluoroethylation of 7-chloro-1,3-dihydro-5-(2-fluorophenyl)-2H-1,4-benzodiazepin-2-one using commercially available 2,2,2-trifluoroethyl trifluoromethanesulfonate (J. Org. Chem. 30, 4322. (1965)) as a trifluoroethylation agent in tetrahydrofuran or ethyl acetate as a solvent in the presence of potassium carbonate under reflux. This finding has led to the completion of the present invention.